Studies will be performed to determine the relationship between the biologic effect of thyroid hormones and their concentration at specific cellular sites. These investigations are designed to elucidate the biochemical basis of thyroid hormone action and the role of thyroid hormones in normal and pathophysiologic processes. Specific attention will be directed to the following aspects: (1) The rate of appearance and disappearance of biochemical parameters of thyroid hormone action will be compared to the concentration of hormone at specific tissue sites in thyroidectomized rats in which thyroid hormone replacement is initiated and terminated. (2) The kinetics of appearance and disappearance of thyroid hormone effect in man will be compared to plasma levels in hypothyroid patients in whom replacement therapy is initiated or terminated. (3) The exchange process of thyroid hormone between pituitary and brain will be analyzed and compared to specific tissue effects of the thyroid hormones. (4) The nature of recently discovered thyroid hormone-protein complexes in plasma and tissue will be analyzed using standard techniques of protein and polypeptide chemistry. The possibility that such protein-hormone complexes may serve as the initiators of hormone action will be tested. (5) Factors influencing the rate of conversion of thyroxine to triiodothyronine will be examined in man and rats.